| 51. |
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| 52. |
- Cao, Zhixing, et al.
(författare)
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Multi-scale data-driven engineering for biosynthetic titer improvement
- 2020
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Ingår i: Current Opinion in Biotechnology. - : Elsevier BV. - 0958-1669 .- 1879-0429. ; 65, s. 205-212
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Forskningsöversikt (refereegranskat)abstract
- Industrial biosynthesis is a very complex process which depends on a range of different factors, from intracellular genes and metabolites, to extracellular culturing conditions and bioreactor engineering. The identification of species that improve the titer of some reaction is akin to the task of finding a needle in a haystack. This review aims to summarize state-of-the-art biosynthesis titer improvement on different scales separately, particularly regarding the advancement of metabolic pathway rewiring and data-driven process optimization and control. By integrating multi-scale data and establishing a mathematical replica of a real biosynthesis, more refined quantitative insights can be gained for achieving a higher titer than ever.
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| 53. |
- Chen, Baoqing, et al.
(författare)
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The Long Noncoding RNA CCAT2 Induces Chromosomal Instability Through BOP1-AURKB Signaling
- 2020
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 159:6, s. 2146-2162
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Tidskriftsartikel (refereegranskat)abstract
- Background & AimsChromosomal instability (CIN) is a carcinogenesis event that promotes metastasis and resistance to therapy by unclear mechanisms. Expression of the colon cancer–associated transcript 2 gene (CCAT2), which encodes a long noncoding RNA (lncRNA), associates with CIN, but little is known about how CCAT2 lncRNA regulates this cancer enabling characteristic.MethodsWe performed cytogenetic analysis of colorectal cancer (CRC) cell lines (HCT116, KM12C/SM, and HT29) overexpressing CCAT2 and colon organoids from C57BL/6N mice with the CCAT2 transgene and without (controls). CRC cells were also analyzed by immunofluorescence microscopy, γ-H2AX, and senescence assays. CCAT2 transgene and control mice were given azoxymethane and dextran sulfate sodium to induce colon tumors. We performed gene expression array and mass spectrometry to detect downstream targets of CCAT2 lncRNA. We characterized interactions between CCAT2 with downstream proteins using MS2 pull-down, RNA immunoprecipitation, and selective 2′-hydroxyl acylation analyzed by primer extension analyses. Downstream proteins were overexpressed in CRC cells and analyzed for CIN. Gene expression levels were measured in CRC and non-tumor tissues from 5 cohorts, comprising more than 900 patients.ResultsHigh expression of CCAT2 induced CIN in CRC cell lines and increased resistance to 5-fluorouracil and oxaliplatin. Mice that expressed the CCAT2 transgene developed chromosome abnormalities, and colon organoids derived from crypt cells of these mice had a higher percentage of chromosome abnormalities compared with organoids from control mice. The transgenic mice given azoxymethane and dextran sulfate sodium developed more and larger colon polyps than control mice given these agents. Microarray analysis and mass spectrometry indicated that expression of CCAT2 increased expression of genes involved in ribosome biogenesis and protein synthesis. CCAT2 lncRNA interacted directly with and stabilized BOP1 ribosomal biogenesis factor (BOP1). CCAT2 also increased expression of MYC, which activated expression of BOP1. Overexpression of BOP1 in CRC cell lines resulted in chromosomal missegregation errors, and increased colony formation, and invasiveness, whereas BOP1 knockdown reduced viability. BOP1 promoted CIN by increasing the active form of aurora kinase B, which regulates chromosomal segregation. BOP1 was overexpressed in polyp tissues from CCAT2 transgenic mice compared with healthy tissue. CCAT2 lncRNA and BOP1 mRNA or protein were all increased in microsatellite stable tumors (characterized by CIN), but not in tumors with microsatellite instability compared with nontumor tissues. Increased levels of CCAT2 lncRNA and BOP1 mRNA correlated with each other and with shorter survival times of patients.ConclusionsWe found that overexpression of CCAT2 in colon cells promotes CIN and carcinogenesis by stabilizing and inducing expression of BOP1 an activator of aurora kinase B. Strategies to target this pathway might be developed for treatment of patients with microsatellite stable colorectal tumors.
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| 54. |
- Chen, Chang, et al.
(författare)
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Untargeted screening of unknown xenobiotics and potential toxins in plasma of poisoned patients using high-resolution mass spectrometry: Generation of xenobiotic fingerprint using background subtraction
- 2016
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Ingår i: Analytica Chimica Acta. - : ELSEVIER SCIENCE BV. - 0003-2670 .- 1873-4324. ; 944, s. 37-43
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Tidskriftsartikel (refereegranskat)abstract
- A novel analytical workflow was developed and applied for the detection and identification of unknown xenobiotics in biological samples. High-resolution mass spectrometry (HRMS)-based data-independent MSE acquisition was employed to record full scan MS and fragment spectral datasets of test and control samples. Then, an untargeted data-mining technique, background subtraction, was utilized to find xenobiotics present only in test samples. Structural elucidation of the detected xenobiotics was accomplished by database search, spectral interpretation, and/or comparison with reference standards. Application of the workflow to analysis of unknown xenobiotics in plasma samples collected from four poisoned patients led to generation of xenobiotic profiles, which were regarded as xenobiotic fingerprints of the individual samples. Among 19 xenobiotics detected, 11 xenobiotics existed in a majority of the patients plasma samples, thus were considered as potential toxins. The follow-up database search led to the tentative identification of azithromycin (X5), alpha-chaconine (X9) and penfluridol (X12). The identity of X12 was further confirmed with its reference standard. In addition, one xenobiotic component (Y5) was tentatively identified as a penfluridol metabolite. The remaining unidentified xenobiotics listed in the xenobiotic fingerprints can be further characterized or identified in retrospective analyses after their spectral data and/or reference compounds are available. This HRMS-based workflow may have broad applications in the detection and identification of unknown xenobiotics in individual biological samples, such as forensic and toxicological analysis and sport enhancement drug screening. (C) 2016 Elsevier B.V. All rights reserved.
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| 55. |
- Chen, Hui, et al.
(författare)
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Age- and sex-specific modifiable risk factor profiles of dementia : evidence from the UK Biobank
- 2023
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 38:1, s. 83-93
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Tidskriftsartikel (refereegranskat)abstract
- Dementia constitutes a worldwide concern. To characterize the age- and sex-specific modifiable risk factor profiles of dementia, we included 497,401 UK Biobank participants (mean age = 56.5 years) without dementia at baseline (2006–2010) and followed them until March 2021. Cox proportional hazard models were used to estimate the age- and sex-specific hazard ratios (HRs) of incident dementia associated with socioeconomic (less education and high Townsend deprivation index), lifestyle (non-moderate alcohol intake, current smoking, suboptimal diet, physical inactivity, and unhealthy sleep duration), and health condition factors (hypertension, diabetes, cardiovascular diseases, and depressive symptoms). We also calculated the population attributable fractions (PAFs) of these factors. During follow-up (mean = 11.6 years), we identified 6564 dementia cases. HRs for the risk factors were similar between the sexes, while most factors showed stronger associations among younger participants. For example, the HRs of smoking were 1.74 (95% CI: 1.23, 2.47) for individuals aged < 50 years, and 1.18 (1.05, 1.33) for those aged ≥ 65 years. Overall, 46.8% (37.4%, 55.2%) of dementia cases were attributable to the investigated risk factors. The PAFs of the investigated risk factors also decreased with age, but that for health condition risk factors decreased with lower magnitude than socioeconomic and lifestyle risk factors. The stronger associations and greater PAFs of several modifiable risk factors for dementia among younger adults than older participants underscored the importance of dementia prevention from an earlier stage across the adult life course.
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| 56. |
- Chen, Hui, et al.
(författare)
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Association of Long-Term Body Weight Variability With Dementia : A Prospective Study
- 2021
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 77:10, s. 2116-2122
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Tidskriftsartikel (refereegranskat)abstract
- Background: Body weight variability (BWV) refers to intraindividual weight loss and gain over a period. The association of long-term BWV with dementia remains unclear and whether this association is beyond body weight change is undetermined.Methods: In the Health and Retirement Study, a total of 5 547 dementia-free participants (56.7% women; mean [SD] age, 71.1 [3.2] years) at baseline (2008) were followed up to 8 years (mean = 6.8 years) to detect incident dementia. Body weight was self-reported biennially from 1992 to 2008. BWV was measured as the coefficient of variation utilizing the body weight reported 9 times across 16 years before baseline. Cox-proportional hazard model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI).Results: Among the 5 547 participants, a total of 427 incident dementia cases were identified during follow-up. Greater long-term BWV was significantly associated with a higher risk of dementia (HR comparing extreme quartiles: 2.01, 95% CI: 1.48-2.72; HR of each SD increment: 1.21, 95% CI: 1.10-1.32; p-trend < .001) independent of mean body weight and body weight change. This significant association was even observed for BWV estimated approximately 15 years preceding dementia diagnosis (HR of each SD increment: 1.13, 95% CI: 1.03-1.23) and was more pronounced for that closer to diagnosis.Conclusion: Our prospective study suggested that greater BWV may be a novel risk factor for dementia.
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| 57. |
- Chen, Hui, et al.
(författare)
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Associations of the Mediterranean-DASH Intervention for Neurodegenerative Delay diet with brain structural markers and their changes
- 2023
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Ingår i: Alzheimer's & Dementia. - 1552-5260 .- 1552-5279.
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The associations of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet with brain structural changes are unclear.METHODS: Among 26,466 UK Biobank participants, a 15-point MIND score was calculated from 24-hour diet recalls from 2009 to 2012. We assessed its associations with 17 magnetic-resonance-derived brain volumetric markers and their longitudinal changes and explored whether genetic factors modify the associations.RESULTS: Higher MIND adherence was associated with larger volumes of thalamus, putamen, pallidum, hippocampus, and accumbens (beta per 3-unit increment ranging from 0.024 to 0.033) and lower white matter hyperintensities (P-trends < 0.05), regardless of genetic predispositions of Alzheimer's disease. MIND score was not associated with their longitudinal changes (P > 0.05) over a median of 2.2 years among participants with repeated imaging assessments (N = 2963), but was associated with slower atrophy in putamen (beta: 0.026, P-trend = 0.044) and pallidum (beta: 0.030, P-trend = 0.033) among APOE ε4 non-carriers (N = 654).DISCUSSION: The MIND diet showed beneficial associations with certain brain imaging markers, and its associations with long-term brain structural changes warrants future investigation.
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| 58. |
- Chen, Lei, et al.
(författare)
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Recent advances in the development of sesquiterpenoids in the treatment of type 2 diabetes
- 2019
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Ingår i: Trends in Food Science & Technology. - : ELSEVIER SCIENCE LONDON. - 0924-2244 .- 1879-3053. ; 88, s. 46-56
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Forskningsöversikt (refereegranskat)abstract
- Background: Treatment of type 2 diabetes mellitus (T2DM) through dietary terpenoids is receiving a promising interest and sesquiterpenoids' importance for food and pharmaceutical industries is mainly based on the existed scientific works. Scope and approach: Sesquiterpenoids might contribute to prevent or delay T2DM by inhibiting key enzymes relevant for hyperglycemia, modulating beta-cells function, targeting insulin signaling route, etc. Sesquiterpenoids also have been demonstrated to stimulate glucose uptake by enhancing glucose transport, repressing glucose production, or improving lipid metabolism. Key findings and conclusions: In this review, we summarized the latest developments of sesquiterpenoids in the treatment of type 2 diabetes as well as sesquiterpenoids-rich herbs against key enzymes relevant to hyperglycemia, and discussed their underlying molecular mechanisms of anti-diabetic potential. We also suggested a better evaluation of the pharmacological profile of sesquiterpenoids and their derivate with a clear-cut choice of possible human pathologies.
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| 59. |
- Chen, Wenjun, et al.
(författare)
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A typological framework of non-floodplain wetlands for global collaborative research and sustainable use
- 2022
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Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 17:11
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Forskningsöversikt (refereegranskat)abstract
- Non-floodplain wetlands (NFWs) are important but vulnerable inland freshwater systems that are receiving increased attention and protection worldwide. However, a lack of consistent terminology, incohesive research objectives, and inherent heterogeneity in existing knowledge hinder cross-regional information sharing and global collaboration. To address this challenge and facilitate future management decisions, we synthesized recent work to understand the state of NFW science and explore new opportunities for research and sustainable NFW use globally. Results from our synthesis show that although NFWs have been widely studied across all continents, regional biases exist in the literature. We hypothesize these biases in the literature stem from terminology rather than real geographical bias around existence and functionality. To confirm this observation, we explored a set of geographically representative NFW regions around the world and characteristics of research focal areas. We conclude that there is more that unites NFW research and management efforts than we might otherwise appreciate. Furthermore, opportunities for cross-regional information sharing and global collaboration exist, but a unified terminology will be needed, as will a focus on wetland functionality. Based on these findings, we discuss four pathways that aid in better collaboration, including improved cohesion in classification and terminology, and unified approaches to modeling and simulation. In turn, legislative objectives must be informed by science to drive conservation and management priorities. Finally, an educational pathway serves to integrate the measures and to promote new technologies that aid in our collective understanding of NFWs. Our resulting framework from NFW synthesis serves to encourage interdisciplinary collaboration and sustainable use and conservation of wetland systems globally.
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| 60. |
- Chen, Xin, 1980, et al.
(författare)
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Optimal and Efficient Power Allocation for OFDM Non-Coherent Cooperative Transmission
- 2012
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Ingår i: IEEE Wireless Communications and Networking Conference, WCNC. - 1525-3511. - 9781467304375 ; , s. 1584-1589
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Konferensbidrag (refereegranskat)abstract
- In this paper, we study the subchannel (SC) power allocation for orthogonal frequency division multiplexing (OFDM) multiple access points (APs) systems with non-coherent cooperative transmission. The objective is to maximize the total capacity under per-AP power constraints. It can be proved that the optimal solution can be obtained by the combination of an optimal SC partition search and the power allocation across SCs for each feasible partition. Existing work exhaustively searched the optimal SC partition and used Lagrange dual method to compute the power allocation across SCs. Since the entire complexity increases exponentially with the number of SCs, the existing method is unsuitable for practical implementation. In this paper, we propose a novel optimal power allocation algorithm for non-coherent cooperative transmission with a much lower complexity. Firstly, a concept of “cut-off SC” is proposed for searching the optimal SC partition. Then, an efficient optimal power allocation algorithm across SCs is proposed for any given cut-off SC. Simulation results demonstrate that the proposed algorithm is optimal with a polynomial complexity, and ends within an acceptable number of iterations.
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